Does Pre-CAR-T Cyclophosphamide Worsen Outcomes in MM?

By Patrick Daly - Last Updated: June 8, 2023

Alkylators, such as cyclophosphamide, are often included in bridging therapy (BT) regimens used to maintain disease control in patients with multiple myeloma (MM) undergoing chimeric antigen receptor (CAR) T-cell therapy. To establish optimal cyclophosphamide in BT, researchers compared 3 administrated schedules used at their center: hyperfractionated inpatient regimens, once-weekly outpatient regimens, and non-cyclophosphamide regimens.

Based on their analysis, the researchers reported hyperfractionated administration did not appear to improve disease control. Alternatively, it was associated with longer post-CAR-T infusion platelet count recovery and worse overall survival (OS). Findings from the study were presented in Transplantation and Cellular Therapy.

The analysis included 64 unique patients with MM and 70 cases of bridging therapies, of which 29 (41%) included hyperfractionated cyclophosphamide with inpatient dosing every 12-24 hours or as a continuous intravenous infusion, 23 (33%) included weekly cyclophosphamide (as in KPd or KCd), and 18 (26%) did not include cyclophosphamide.

More Intense Cyclophosphamide Linked to Poorer MM Outcomes

The report noted that median total concentrations of cyclophosphamide during BT were 2100 mg/m2 in the hyperfractionated group, 615 mg/m2 in the weekly group, and 0 mg/m2 in the non-cyclophosphamide group.

According to the authors, a ≥25% or ≥100 mg/L increase of involved free light chain (iFLC) levels occurred in comparable proportions across groups at 52% for hyperfractionated, 39% for weekly, and 28% for non-cyclophosphamide (P=.25).

In 61 cases of BT that were followed by CAR-T for MM, PFS and neutrophil recovery times were comparable. However, the following outcomes differed by cyclophosphamide intensity:

Hyperfractioned Weekly Non-Cyclophosphamide
Vein-to-Vein Time 45 days 39 days 46.5 days
Platelet Recovery Time 64 days 42 days 12 days
Median OS 15.3 months 30.0 months Not reached


The authors summarized, “Given the rarity of objective disease responses to chemotherapy in relapsed/refractory MM our analysis suggests that hyperfractionated [cyclophosphamide] regimens do not outperform once-weekly [cyclophosphamide] regimens for most patients who require BT before CAR-T therapy.”

Related: Cilta-Cel in Earlier Treatment Lines for Refractory Multiple Myeloma

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